New derivatives of xanthenone-4-acetic acid: Synthesis, pharmacological profile and effect on TNF-α and NO production by human immune cells

New derivatives of xanthenone-4-acetic acid, bearing an alkoxy chain of variable length and a basic moiety, were synthesised in order to test the influence of this additional function on antitumour activity. The introduction of bulky substituents carrying a basic nitrogen seems to be somewhat tolerated, since for some of the compounds the enhancement of lytic potential of human monocytes was comparable to that of the reference molecule DMXAA. The induction of the release of TNF-α and nitric oxide by human monocytes, as well as the hypothesis of a potentiation of the activity of lipopolysaccharide in the induction of those cytotoxic factors, was also evaluated. In this respect, the most interesting compound (6a) exhibited the same spectrum of biological activity shown by DMXAA and seems therefore to be endowed with the same mechanism of action of the reference compound.

New derivatives of xanthenone-4-acetic acid were synthesised and tested for their antitumour effects.Figure optionsDownload as PowerPoint slide